Synthesis of pyrrolidines and tetrahydro-1H-azepines from 4-aryl-1-benzoyl(ethoxycarbonyl)methyl-1-methyl-1,2,3,6-tetrahydropyridinium halides

Article abstract of DOI:10.1007/s10593-007-0219-2

4-Aryl-1,2,3,6-tetrahydropyridinium quaternary salts which have a benzoylmethyl or ethoxycarbonylmethyl group on atom N-1 generate N-ylides when heated in the presence of NaH and they can rearrange in situ with contraction or expansion of the six-membered

Full text of DOI:10.1007/s10593-007-0219-2

Chemistry of Heterocyclic Compounds, Vol. 43, No. 11, 2007
SYNTHESIS OF PYRROLIDINES
AND TETRAHYDRO-1H-AZEPINES
FROM 4-ARYL-1-BENZOYL(ETHOXY-
CARBONYL)METHYL-1-METHYL-
1,2,3,6-TETRAHYDROPYRIDINIUM
HALIDES
S. A. Soldatova, G. S. Gimranova, Zh. A. Mamyrbekova,
K. B. Polyanskii, S. V. Akbulatov, and A. T. Soldatenkov
4-Aryl-1,2,3,6-tetrahydropyridinium quaternary salts which have
a
benzoylmethyl or
ethoxycarbonylmethyl group on atom N-1 generate N-ylides when heated in the presence of NaH and
they can rearrange in situ with contraction or expansion of the six-membered heterocycle to give
substituted pyrrolidines (as a result of a [2,3]-sigmatropic rearrangement) or 1H-tetrahydroazepine
derivatives (via Stevens rearrangement). The presence of an aryl substituent at position C-4 in the
tetrahydropyridine ring allows to avoid the formation of elimination products and changes the direction
of the reaction towards the preparation of the tetrahydroazepines.
Keywords: 4-aryl-1-benzoyl(ethoxycarbonyl)methyl-1,2,3,6-tetrahydropyridinium halides, N-ylides,
pyrollidines, tetrahydro-1H-azepines, 1,2-shift, sigmatropic rearrangement.
In the presence of base, N-methyl-N-phenacyl-1,2,3,6-tetrahydropyridinium halides are converted to
N-ylide systems which can rearrange with contraction of the six-membered heterocycle to five-membered
forming N-alkyl-2-benzoyl-3-vinylpyrrolidines [1, 2]. Exchange of the N-phenacyl fragment in the starting
quaternary tetrahydropyridinium salts for N-(alkoxycarbonyl)methyl also stabilizes the intermediate ylides and
leads to derivatives of the natural α-amino acid proline [3-7] which may be important from the viewpoint of
biological activity. Key features in the studies [1-7] are as follows: firstly only C-unsubstituted
tetrahydropyridines were used as the basic starting materials; secondly a high diastereoselectivity (95%) was
found in the substituted pyrrolidines formed; and finally the basic electrophilic [2,3]-sigmatropic rearrangement
was accompanied by up to 45% β-elimination with opening of the heterocycle and the formation of
dialkylaminopenta-2,4-dienes.
In connection with our systematic investigation of the chemistry of 4-aryl-substituted
tetrahydropyridines and related compounds [8, 9] we decided to study the effect of an aryl substituent in the
quaternary tetrahydropyridinium salts on the route of their reaction in the presence of base.
__________________________________________________________________________________________
People's Friendship University of Russia, Moscow 117198; e-mail: spektrudn@yahoo.com. Translated
from Khimiya Geterotsiklicheskikh Soedinenii, No. 11, pp. 1670-1676, November, 2007. Original article
submitted July 21, 2006.
1420
0009-3122/07/4311-1420©2007 Springer Science+Business Media, Inc.

R
N
R
R
ClCH2COOEt
BrCH2COPh
+
N
+
N
Cl
Br
Me
CH2COOEt
Me
CH2COPh
Me
1a-c
2a,b
3a-c
R
R
NaH
NaH
H-c
+
H-b
H-a
COR1
N
N
Me
COOEt
Me
4a-d
5a-c
1-3, 5 a R = H, b R = Me, c R = Br; 4 a R = H, R1 = Ph, b R = Br, R1 = Ph,
c R = H, R1 = OEt, d R = Me, R1 = OEt
With this in mind we have used the 4-aryltetrahydropyridines 1a-c to prepare the quaternary salts 2a,b
and 3a-c which served as intermediate ylide precursors. The rearrangements were carried out by refluxing the
indicated salts in the presence of sodium hydride in dioxane for 2-3 h. In the case of the phenacylbromides 2a,b
column chromatography of the reaction mixture on silica gel led to the separation of only the pyrrolidines 4a,b
1
in yields of 35 and 15% respectively. According to H NMR data these pyrrolidines were obtained as an
unresolved mixture of two diastereomers in the ratio 1:1 (for R = H) or 1.5:1 (for R = Br). A comparative
1
analysis of the H NMR spectra of the mixture of diastereoisomers 4a,b and the individual cis-(2-H,3-H)
diastereomers having a similar structure [3-6] shows that the signals of the all of the aliphatic analogous protons
of the trans-(2-COPh, 3-CH=CH2) diastereomers 4a,b are significantly shifted to low field by up to 0.38 ppm
when compared with the signals of the corresponding cis-forms.
Hence the introduction of an aryl substituent at position C-4 of the heterocycle in the N-phenacyl salts
2a,b leads to a marked lowering of the diastereoselectivity of the [2,3]-sigmatropic rearrangement of the
tetrahydropyridine nucleus to the pyrrolidine.
In the analogous work up of all quaternary salts 3a-c the expected pyrrolidines were obtained in 39 (4c)
and 58% (4d) yields respectively. Chromato-mass spectrometric analysis of the mixture of products obtained
from the quaternary salt 3c showed that the corresponding pyrrolidine was obtained in trace amounts. In
addition, in all three cases the azepine derivatives 5a-c, products of expansion of the tetrahydropyridine ring,
were obtained (see previous report [10] regarding the formation of compound 5a). In the case of the phenyl or
4-tolyl substituent (salts 3a,b) the yield of the tetrahydroazepine 5a,b was low (25 and 5% respectively).
However, upon changing to the quaternary salt 3c which has a 4-bromophenyl substituent, the yield of the
tetrahydroazepine 5c increased to 60%. The structure of the azepine derivatives 5a-c was confirmed by their 1H
and 13C NMR spectra in which signals of all of the protons and carbon atoms of the Cquat–CH2–CH2N and
C
quat=CH–CH2CH(NMe)COOEt links were observed (see Experimental). The mass spectra showed low intensity
molecular ion peaks M+ as well as fragment ion peaks formed by fission of a methyl or ethyl
1421

group from M+. The maximum intensity peak is assigned to the fragment arising from fission of the
[CHCOOEt]+ fragment and a hydrogen atom from M+. The IR spectra of the tetrahydroazepine shows strong
absorption peaks for the C=O group in the region 1727-1730 cm-1.
R
R
R
R1
R1
B
route a
H
H
2, 3
O
C
C
– BX
O
N+
N+
+
N
–
CH
route b
B-endo
B-exo
A
COR1
R
R
R
R
+
N
R1
R1
.
.
N
CH ..
–
O
O
N
N
O
R1
O
R1
trans-4a–c
5a–c
cis-4a–d
C
It should be noted a similar reaction of N-methyl-N-nitrobenzyl(or N-phenacyl)-6-hydroxy-1,2,3,4-
tetrahydroisoquinolinium bromides to tetrahydrobenzazepines has been reported in [11]. However, this work
pointed to a dominating effect of the 6-OH group in the benzene ring for expantion of the piperidine ring (only
via the intermediate quinoid form). Only β-elimination-decyclization processes occurred in the absence of this
hydroxyl group!
Hence we have shown in our work that the introduction of a 4-aryl substituent into the
tetrahydropyridine ring can lead to a novel route for reaction of the heterocycle, i.e. to a [1,2]-shift with
formation of the seven-membered aza ring. For all of the experiments with salts 2 and 3 it should be stressed
that, firstly, products of Hofmann [12] decyclization were not identified and, secondly, the expected and
unexpected rearrangements of the tetrahydropyridine ring took place only via its allylamine fragment.
We finally consider the possible reactions mechanisms for salts 2 and 3. In the presence of base they
firstly form the highly reactive ylides (A). The latter in the case of transitions states (B-endo, B-exo; route a) can
be transformed by a [2,3]-sigmatropic rearrangement to cis- and/or trans-diastereomeric pyrrolidines 4 [13]
thanks to the greater (B-endo) or lesser (B-exo) degree of secondary orbital control and also due to the electronic
and steric interactions between the acyl group and the benzene ring. At the same time, the presence of the
arylallylamino fragment and strongly stabilizing N-ylide N-ethoxycarbonyl group permits a second reaction
path. In this [1,2]-shift route b there occur dissociation-recombination processes transforming the
-
>N+(C HCOR)CH2-6 group of the ylides (A) via the close biradical states (C) [13] to the >N–CH(COR)CH2-3
group in molecule 5. This anionic [1,2]-shift (Stevens rearrangement) leads in this case to the formation of a
stable seven-membered heterosystem.
1422

EXPERIMENTAL
1H and 13C NMR spectra were obtained on a Bruker WM-400 instrument (400 and 100 MHz
respectively) using DMSO-d6 (compounds 2a,b and 3a-c) or CDCl3 (compounds 4a-d and 5a-c) with TMS as
internal standard and mass spectra on a Finnigan MAT 95XL chromato-mass spectrometer with ionization
energy 70 eV. IR spectra were taken on a Specord IR-75 spectrophotometer using a KBr matrix (quaternary salts
2a,b, 3a-c) or paraffin oil (compounds 4a-d, 5a-c). Chemapol L 40/100 micron silica gel was used in the
preparative column chromatography. Monitoring of the reaction course and the purity of the synthesized
compounds was carried out by TLC on Silufol UV-254 plates.
Compounds 1a-c were prepared as reported in [14].
Synthesis of Quaternary Salts 2a,b and 3a-c. ω-Bromoacetophenone (2.39 g, 12 mmol) (synthesis of
salts 2a,b) or ethyl chloroacetate (1.42 g, 12 mmol) (synthesis of salts 3a-c) were added gradually to a solution
of 4-aryl-1-methyl-1,2,3,6-tetrahydropyridine 1a-c (12 mmol) in absolute benzene (50 ml). The mixture was
held for 3 days at 20ºC. The precipitate was separated and purified by recrystallization from acetone to give the
reaction product as colorless crystals.
1-Methyl-1-(2-oxo-2-phenylethyl)-4-phenyl-1,2,3,6-tetrahydropyridinium Bromide (2a). Yield
1
3.21 g (75%); mp 205-208ºC. IR spectrum, ν, cm-1: 1688 (C=O). H NMR spectrum, δ, ppm (J, Hz): 2.95 (2Н,
br. s, 3-CH2); 3.37 (3Н, s, CH3); 3.92 and 4.06 (each 1H, both m, 2-CH2); 4.42 and 4.53 (each 1H, both br. d,
J = 11.8, 6-СН2); 5.49 and 5.52 (each 1H, both d, J = 17.5, NСН2СО); 6.22 (1Н, br. s, 5-СН); 7.38–7.74 (8Н, m,
Нarom); 8.04 (2Н, d, J = 7.48, ОCC6H5). Found, %: Br 21.44; N 3.66. C20H22BrNO. Calculated, %: Br 21.46; N
3.76.
4-(4-Bromophenyl)-1-methyl-1-(2-oxo-2-phenylethyl)-1,2,3,6-tetrahydropyridinium Bromide (2b).
Yield 3.55 g (81%), mp 167-168ºC. IR spectrum, ν, cm-1: 1690 (C=O). 1H NMR spectrum, δ, ppm (J, Hz): 2.93
(2Н, br. s, 3-CH2); 3.36 (3Н, s, CH3); 3.88 and 4.01 (each 1H, both m, 2-CH2); 4.38 and 4.48 (each 1H, both
br. d, J = 11.7, 6-СН2); 5.38 and 5.44 (each 1H, both d, J = 17.6, NСН2СО); 6.24 (1Н, br. s, 5-СН); 7.48 and
7.58 (each 2H, AA'BB' spectrum, J = 8.35, Нarom); 7.61 (2Н, m, OCC6H5); 7.74 (1Н, t, J = 7.46 and J = 7.31,
ОСC6H5); 8.02 (2Н, d, J = 7.52, ОСC6H5). Found, %: Br 35.39; N 3.0. C20H21Br2NO. Calculated, %: Br 35.42;
N 3.10.
1-Ethoxycarbonylmethyl-1-methyl-4-phenyl-1,2,3,6-tetrahydropyridinium Chloride (3a). Yield 2.1
g (62%); mp 167-168ºC (dec.). IR spectrum, ν, cm-1: 1740 (C=O). 1H NMR spectrum, δ, ppm (J, Hz): 1.24 (3Н,
t, J = 7.2, С–CH3); 2.88 (2Н, br. s, 3-СН2); 3.30 (3Н, s, N–CH3); 3.90 (2Н, m, 2-СН2); 4.23 (2Н, q, J = 7.11,
ОСН2); 4.33 and 4.47 (each 1H, both br. d, J = 16.45, 6-СН2); 4.67 and 4.72 (each 1H, both d, J = 16.6,
NCH2CO); 6.18 (1Н, br. s, 5-СН); 7.26–7.57 (5Н, m, C6H5). Found, %: Сl 11.63; N 4.91. C16H22СlNO2.
Calculated, %: Сl 11.99; N 4.74.
1-Ethoxycarbonylmethyl-1-methyl-4-(4-methylphenyl)-1,2,3,6-tetrahydropyridinium Chloride (3b).
Yield 2.51 g (78%); mp 156-158ºC. IR spectrum, ν, cm-1: 1748 (C=O). 1H NMR spectrum, δ, ppm (J, Hz): 1.26
(3Н, t, J = 7.00, ОСН2CH3); 2.30 (3Н, s, АrCH3); 2.88 (2Н, br. s, 3-СН2); 3.29 (3Н, s, N–CH3); 3.90 (2Н, m,
2-СН2); 4.25 (2Н, q, J = 7.02, О–СН2); 4.23 and 4.26 (each 1H, both d, J = 16.5, NCH2CO); 4.30 and 4.41
(each 1H, both br. d, J = 16.20, 6-СН2); 6.12 (1Н, br. s, Н-5); 7.21 and 7.40 (each 2H, AA'BB' spectrum,
J = 7.93, Нarom). Found, %: Сl 11.40; N 4.5. C17H24СlNO2. Calculated, %: Сl 11.44; N 4.52.
4-(4-Bromophenyl)-1-ethoxycarbonylmethyl-1-methyl-1,2,3,6-tetrahydropyridinium Chloride (3c).
Yield 2.36 g (80%); mp 172-174ºC. IR spectrum, ν, cm-1: 1742 (C=O). 1H NMR spectrum, δ, ppm (J, Hz): 1.24
(3Н, t, J = 7.11, ОСН2CH3); 2.87 (2Н, br. s, 3-СН2); 3.31 (3Н, s, N–CH3); 3.92 (2Н, m, 2-СН2); 4.22 (2Н, q,
J = 7.10, О–СН2); 4.34 and 4.47 (each 1H, both br. d, J = 16.31, 6-СН2); 4.67 and 4.73 (each 1H, both d,
J = 17.0, NCH2CO); 6.22 (1Н, br. s, 5-СН); 7.47 and 7.57 (each 2H, AA'BB' spectrum, J = 8.47, Нarom). Found,
%: N 3.8. C16H21BrСlNO2. Calculated, %: N 3.74.
1423

Transformation of the Quaternary Salts 2a,b and 3a-c to the Pyrollidines 4a-d and Tetrahdro-1H-
azepines 5a-c. Sodium hydride (0.14 g, 3.4 mmol as a 60% suspension in absolute toluene) was added to a
suspension of the quaternary salt (2a,b, 3a-c) (3.4 mmol) in absolute dioxane (30 ml) under a nitrogen
atmosphere. After refluxing for 2 h, methanol (1 ml) was added, and the solvent was distilled of in vacuo. The
residue was treated with water (50 ml) and the organic base was extracted with ether. The extract was washed
twice with water, dried over anhydrous MgSO4, and evaporated in vacuo. The residue was separated and purified
by column chromatography on silica gel using a gradient of hexane–ethyl acetate from 1:0 to 1:10.
2-Benzoyl-3-ethenyl-1-methyl-3-phenylpyrrolidine (4a) was separated as a mixture of two
diastereoisomers with a 1:1 ratio of cis-(2-COPh, 3-CH=CH2) to trans-(2-COPh, 3-CH=CH2) isomers from
1H NMR data. Colorless, thick oil. Yield 0.4 g (35%). IR spectrum, ν, cm-1: 1683 (C=O). 1H NMR spectrum, δ,
ppm (J, Hz) (spectrum shows a double set of aliphatic protons signals for the cis/trans isomers: assignment of
the proton signals of the cis form was made by analysis of the spectra of analogous pyrrolidines [3-6]; specific
vinyl group protons are given in the scheme for the synthesis of compounds 4a-d): 2.12/2.28 (0.5Н/0.5Н m/m,
4-СН2); 2.41/2.47 (1.5Н/1.5Н, s/s, N–CH3); 2.66/2.83 (0.5Н/0.5Н, m/m, 4-СН2); 2.87/2.97 (0.5Н/0.5Н, m/m,
5-СН2); 3.23/3.31 (0.5Н/0.5Н, dt/dt, J = 8.13 and J = 1.62, 5-СН2); 4.68/4.71 (0.5Н/0.5Н, s/s, 2-СН); 4.91/5.08
(0.5Н/0.5Н, dd, J = 17.26 and J = 1.4, Н-а); 5.01/5.19 (0.5Н/0.5Н, dd, J = 10.67 and J = 1.5, Н-b); 5.87/6.22
(0.5Н/0.5Н, dd, J = 17.26 and J = 10.67, Н-с); 6.95-7.79 (10Н, m/m, C6H5). Mass spectrum, m/z: 293 [M+].
Found, %: С 77.9; Н 6.50; N 4.71. С19Н19NO. Calculated, %: С 77.79; Н 6.53; N 4.77.
2-Benzoyl-3-(4-bromophenyl)-3-ethenyl-1-methylpyrrolidine (4b) was separated as a mixture of two
1
diastereomers with a 1.5:1 ratio of cis- to trans-(2-COPh, 3-CH=CH2) isomers from H NMR data. Colorless,
1
thick oil. Yield 0.18 g (15%). IR spectrum, ν, cm-1: 1701 (C=O). H NMR spectrum, δ, ppm (J, Hz) (spectrum
shows a double set of aliphatic protons signals for the cis/trans isomers): 2.12/2.28 (0.6Н/0.4Н, m/m, 4-СН2);
2.37/2.44 (1.8Н/1.2Н, s/s, N–CH3); 2.67–3.00 (2Н, m, 4-СН2, 5-СН2); 3.20/3.28 (0.6Н/0.4Н, dt/dt, J = 6.73 and
J = 1.8, 5-СН2); 4.68/4.71 (0.6Н/0.4Н, s/s, 2-СН); 4.84/5.03 (0.6Н/0.4Н, dd, J = 16.89 and J = 1.5, Н-а);
4.98/5.16 (0.6Н/0.4Н, dd, J = 10.71 and J = 1.5, Н-b); 5.82/6.17 (0.6Н/0.4Н, dd, J = 16.71 and J = 10.70, Н-с);
6.90–7.96 (9Н, m, Нarom). Mass spectrum, m/z: 371 [M+]. Found, %: С 61.37; Н 4.9; N 3.72. С19Н18ВrNO.
Calculated, %: С 61.30; Н 4.87; N 3.76.
3-Ethenyl-2-ethoxycarbonyl-1-methyl-3-phenylpyrrolidine (4c) was separated as a mixture of two
1
diastereomers with a 4:1 ratio of cis- and trans-(2-COOEt, 3-CH=CH2) isomers from H NMR data. Colorless,
thick oil. Yield 0.34 g (39%). IR spectrum, ν, cm-1: 1731 (C=). 1H NMR spectrum, δ, ppm (J, Hz): 1.24 (3Н, dt,
J = 7.33, ОСН2СН3); 2.28–2.60 (2Н, m, 4-СН2); 2.36/2.40 (2.4Н/0.6Н, s/s, N–CH3); 3.14 (0.8Н, dd, J = 8.0 and
J = 2.1, 5-СН2); 3.24–3.46 (12Н, m, 5-СН2); 3.65/3.67 (0.8Н/0.2Н, s/s, 2-СН), 4.16 (2Н, dq, J = 7.33,
ОСН2Me); 4.70/5.08 (0.8Н/0.2Н, dd, J = 17.40 and J = 1.2, Н-а); 5.02/5.27 (0.8Н/0.2Н, dd, J = 10.71 and
J = 1.2, Н-b); 6.03/6.80 (0.8Н/0.2Н, dd, J = 17.4 and J = 10.7, Н-с); 7.22–7.43 (5Н, m, Нarom). Mass spectrum,
m/z (Irel, %): 259 [M]+ (2), 186 (100), 158 (5), 143 (4), 128 (7), 115 (8), 100 (14), 91 (3), 77 (2), 42 (7). Found,
%: С 74.09; Н 7.92; N 5.33. С16Н21NO2. Calculated, %: С 74.13; Н 8.11; N 5.41.
3-Ethenyl-2-ethoxycarbonyl-1-methyl-3-(4-methylphenyl)pyrrolidine (4d) was separated as a single
cis- (2-COOEt, 3-CH=CH2)-isomer. Colorless, thick oil. Yield 0.45 g (58%). IR spectrum, ν, cm-1: 1742 (C=O).
1H NMR spectrum, δ, ppm (J, Hz): 1.22 (3Н, t, J = 7.25, ОСН2СН3); 2.33 (1Н, m, 4-СН2); 2.29 (3Н, s, С–CH3);
2.36 (3Н, s, N–CH3); 2.42 (1Н, m, 4-СН2); 2.53 (1Н, dt, J = 8.03 and J = 2.2, 5-СН2); 3.12 (1Н, dt, J = 8.00 and
J = 2.1, 5-СН2); 3.61 (1Н, s, 2-СН); 4.13 (2Н, q, J = 7.28, ОСН2Me); 4.66 (1Н, dd, J = 17.41 and J = 1.2, Н-а);
4.98 (1Н, dd, J = 10.70 and J = 1.2, Н-b); 6.00 (1Н, dd, J = 17.40 and J = 10.72, Н-с); 7.05 and 7.36 (each 2H,
AA'BB' spectrum, J = 7.93 and J = 1.1, Нarom). Mass spectrum, m/z: 273 [M+]. Found, %: С 74.72; Н 8.44;
N 5.10. С17Н23NО2. Calculated, %: С 74.69; Н 8.48; N 5.12.
2-Ethoxycarbonyl-1-methyl-5-phenyl-2,3,6,7-tetrahydro-1H-azepine (5a). Yield 0.22 g (25%).
Colorless, thick oil. IR spectrum, ν, cm-1: 1728 (C=O). 1H NMR spectrum, δ, ppm (J, Hz): 1.24 (3Н, t, J = 7.2,
ОСН2СН3); 2.40 (2Н, m, 6-СН2); 2.44 (3Н, s, N–CH3); 2.58–3.00 (4Н, m, 3- and 7-СН2); 3.39 (1Н, br. s, H-2);
1424

4.16 (2Н, q, J = 7.2, ОСН2Me); 5.96 (1Н, br. s, Н-4); 7.20–7.35 (5Н, m, C6H5). 13С NMR spectrum (DMSO-d6),
δ, ppm: 13.8 (С–CH3); 22.5 (6-СН2); 35.6 (3-СН2); 40.0 (N–CH3); 48.7 (7-СН2); 57.8 (7-СН); 60.7 (О–СН2);
119.1 (4-СН); 124.8, 128.0 and 128.4 (C6H5); 134.8 (5-Сquat); 138.0 (Сarom quat); 169.4 (С=О). Mass spectrum,
m/z (Irel, %): 259 [M+] (5), 244 (8), 230 (3), 186 (2), 172 (100), 157 (3), 141 (6), 128 (10), 115 (10), 91 (9), 77
(5), 42 (27). Found, %: С 74.25; Н 8.39; N 5.08. С16Н21NO2. Calculated, %: С 74.13; Н 8.11; N 5.41.
2-Ethoxycarbonyl-1-methyl-5-(4-methylphenyl)-2,3,6,7-tetrahydro-1H-azepine (5b). Yield 0.05 g
1
(5%). Colorless, thick oil. IR spectrum, ν, cm-1: 1730 (C=O). H NMR spectrum, δ, ppm (J, Hz): 1.26 (3Н, t,
J = 7.10, ОСН2СН3); 2.00 (1Н, m, 6-СН2); 2.26 (1Н, m, 6-СН2); 2.32 (3Н, s, ArCH3); 2.46 (3Н, s, N–CH3); 2.62
(1Н, m, 3-СН2); 2.72 (1Н, m, 7-СН2); 2.82 (1Н, dd, J = 10.88 and J = 4.5, 3-СН2); 3.04 (1Н, m, 7-СН2); 3.47
(1Н, br. s, 2-СН); 4.15 (2Н, q, J = 7.05, ОСН2СН3); 5.92 (1Н, br. s, H-4); 7.09 and 7.24 (each 2H, AA'BB'
spectrum, J = 7.83 and J = 1.1, Нarom). Mass spectrum, m/z: 273 [M+]. Found, %: С 74.2; Н 8.16; N 5.2.
С17Н23NO2. Calculated, %: С 74.14; Н 8.15; N 5.09.
1-Methyl-5-(4-bromophenyl)-2-ethoxycarbonyl-2,3,6,7-tetrahydro-1H-azepine (5c). Yield 0.68
(60%). Thick, yellowish oil. IR spectrum, ν, cm-1: 1727 (C=O). 1H NMR spectrum, δ, ppm (J, Hz): 1.26 (3Н, t,
J = 7.04, ОСН2СН3); 2.35–2.41 (2Н, m, 6-СН2); 2.43 (3Н, s, N–CH3); 2.53–2.64 (2Н, m, 3-СН2, 7-СН2); 2.75
(1Н, dd, J = 14.51 and J = 4.90, 3-СН2); 2.98 (1Н, m, 7-СН2); 3.36 (1Н, br. s, 2-СН); 4.16 (2Н, q, J = 7.06,
ОСН2СН3); 5.96 (1Н, br. s, H-4); 7.19 and 7.47 (each 2H, AA'BB' spectrum, J = 7.67 and J = 1.2, Нarom). Mass
spectrum, m/z: 337 [M+]. Found, %: С 56.9; Н 5.90; N 4.16. С16Н20BrNO2. Calculated, %: С 56.82; Н 5.96;
N 4.14.
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